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Publication of proposed new regulations for pharmaceuticals in the environment has been postponed due to challenges in working out solutions and establishing a common framework.
The European Union has been committed for several years to drawing up a strategy on allaying public concerns about contamination of the environment by pharmaceuticals. The strategy on pharmaceuticals in the environment (PIE) would deal in particular with worries among Europeans as well as health professionals and non-governmental organizations (NGOs) about environmental causes of antimicrobial resistance, including untreated waste from plants making antibiotics and their APIs. The objective was that the strategy, due to be published this year by the European Commission (EC), the EU’s Brussels-based executive, would include both legislative and non-regulatory proposals, as laid down in a 2013 EU directive (1) on control of water pollution by pharmaceuticals. The directive stipulates that the EC should propose measures with “a view to reducing discharges, emissions, and losses of [polluting pharmaceutical] substances into the aquatic environment.”
The EC has decided to postpone making proposals for legislative measures, including a decision on whether to go ahead with the controversial option, strongly opposed by the industry, of laying down standards for waste treatment in pharmaceutical plants by extending good manufacturing practice (GMP) to cover environmental controls. After a series of studies by outside consultancies, workshops, and consultations with the public and stakeholders, the last of which was completed in February 2018, the commission was expected at last to fulfil its commitment by publishing a full strategy, including coverage of regulations, and then pressing ahead with its implementation.
“When we met commission officials in early July , it was clear that they were delaying the publication of any proposals on regulations, including any planned legislation on applying GMP to waste management in pharmaceutical plants,” Adela Maghear, pharmaceuticals officer at Health Care Without Harm (HCWH), told Pharmaceutical Technology Europe. “This could mean even more delays in the introduction of legislation on PIE,” commented Maghear, who was in a delegation of NGO representatives visiting the EC.
The splitting of the PIE strategy into two stages, the first without regulations and the second with, will result in the existing EC passing to a new Commission the responsibility of proposing legislation. The new executive, with commissioners appointed by the governments of the EU member states, is due to take over in 2019. The slow pace at which the EC is adopting a PIE strategy is likely to work in favour of the pharmaceutical industry, which has been pushing forward with its own voluntary solutions to environmental problems with pharmaceuticals, especially those related to antimicrobial resistance. It gives the industry the opportunity to demonstrate that the voluntary approach is a viable alternative to regulation.
An Antimicrobial Resistance (AMR) Industry Alliance, a global life-sciences coalition of more than 100 biotech, diagnostics, generic-drug, and research-based biopharmaceutical companies, has been combating AMR through work on the environment, as well as research, easing access to appropriate medicines and appropriate use of pharmaceuticals. In Europe, the three main pharmaceutical associations-European Federation of Pharmaceutical Industries and Associations (EFPIA), Medicines for Europe, and the Association of the European Self-Medication Industry (AESGP)-have set up the Inter-Association Task Force on Pharmaceuticals in the Environment. They have also cofounded the Eco-Pharmaco-Stewardship (EPS), which deals with the entire lifecycles of medicines, taking into account the responsibilities of public services, the pharmaceutical industry itself, environmental experts, health professionals, and patients.
One priority behind EPS activities is the compilation of best industry practices in the management of pharmaceutical manufacturing effluents so that drug producers can minimize the risks to the environment and the spread of AMR. The assumption is that because the production processes for many medicinal producers are broadly similar to each other, potentially dangerous discharges into the environment should be equally controllable, as long as the knowledge about how to limit emissions is uniformly available.
Thirteen members of the AMR Industry Alliance including leading pharmaceutical multinationals such as AstraZeneca, GlaxoSmithKline, Johnson & Johnson, Merck & Co, Pfizer, and Novartis have signed up to a roadmap committing themselves to a number of aims for clean antibiotics production. These aims include establishing a “common framework” for managing antibiotic manufacturing emissions based on “science-driven, risk-based targets for discharge concentrations for antibiotics.”
The work being done by EPS and AMR Alliance will help demonstrate that international good environmental practice standards can be created, which make the use of GMP in the environmental area unnecessary. “We are strongly opposed to the use of GMP in environmental matters because we believe it should remain entirely focused on product quality,” Bengt Mattson, co-chair of the Inter-Association Task Force on PIE, told Pharmaceutical Technology Europe. “The environmental management standard would be entirely different,” he added. “It would be an alternative standard that could ultimately become the basis for a uniform global regulatory initiative.”
Harmonization of legal emission standards
By the time the EC draws up proposals for tighter regulatory controls on emissions from pharmaceutical plants, it is likely to need the data on best practices and concentration thresholds collected by the industry. Because the vast majority of APIs in antibiotics marketed in Europe are produced in India and China, the EU will require harmonized legal emissions standards that can be applied to imported pharmaceuticals in the same way that uniform GMP standards are currently applied to them.
What the EU has achieved by raising product quality through GMP requirements for API imports, India is now looking to the EU to do the same with environment waste controls in Indian pharmaceutical plants. Indian NGOs, health professional groups, and community rights activists sent a joint letter in early July 2018 (2) to the EC claiming that EU action was needed to deal with “the grave environmental and human health crisis” in India linked to the lack of regulatory controls on effluent from the country’s API plants. This issue was causing “rampant” pollution around the country’s pharmaceutical manufacturing hubs such as Hyderabad, which has led to a “huge” AMR problem in India, according to the letter (2). It argued that the only way to tackle the crisis was by the EU extending GMP to include environmental criteria.
Partly as a result of the growing evidence from academic studies connecting AMR to manufacturing waste and the industry’s own collective initiatives on the issue, individual pharmaceutical companies have established their own “clean” or “green” supply chains extending, if necessary, from starting materials and API production to distribution. DSM Sinochem Pharmaceuticals (DSP), a joint Dutch-Chinese venture, has introduced in its plants in China, India, Mexico, and Spain a green fermentative and enzymatic process for antibiotic intermediates (3). In addition to eliminating solvents and achieving low-carbon footprints, the company is also committed to minimizing the release of antimicrobial active ingredients into the environment.
Mylan, one of the world’s largest producers of antibacterial APIs, has switched its plants in Hyderabad to a system of zero-liquid-discharge (ZLD) so that antimicrobial compounds can be kept out of the environment. The technology is being extended to Mylan’s other plants in India.
These pharmaceutical multinationals with audited green APIs supply chains are not only gaining business from international producers of finished medicines. They have also attracted the attention of a number of Scandinavian and other European governments that operate green procurement policies for drugs, particularly antibiotics. However, government buyers of antibiotics and other medicines in bulk as well as pharmaceutical companies purchasing APIs are using different criteria to judge whether the products are adequately green. There is, therefore, a pressing need for harmonization. But this uniformity is unlikely to be achieved until more evidence is available on the biological and chemical mechanisms that create AMR within pharmaceutical plant effluent.
Signatories of the AMR Alliance Roadmap do not expect to be able to determine resistance-based limits on discharge volumes until 2020 at the earliest. These limits will then be used to devise good practice methods. Before it even considers PIE regulations, particularly in relation to AMR, the EU is likely to fund research projects to fill knowledge gaps on the hazards of AMR in the environment, including in manufacturing effluent.
The pharmaceutical industry wants to be able to influence the direction of this research, as well as being closely involved in the deliberations of the new Commission on possible regulations. “There could be a lot of non-legislative initiatives following the [current] Commission’s publication of its strategy document and research will be a big part of these,” noted Mattson. “We can help to define what research is needed. We will also have a lot of information to share with the new Commission-not just on research issues but particularly when it comes to discussing possible regulations.”
Once regulations are in place, the next stage will be efforts to extend the principles behind them to outside Europe so that they fit into a harmonized global approach to problems with pharmaceutical plant waste.
“We’ve still got a long way to go,” Mattson said. “The length of time it has taken for the EU to draw up a PIE strategy shows the difficulties of working out solutions. There will have to be a lot of discussion before a common framework can be established.”
1. EU Directive 2013/39/EU, Priority Substances in the Field of Water Pollution(Brussels, 12 Aug. 2013).
2. Gamana, Hyderabad, Community Environmental Monitoring, Chennai, and Other Groups, “Letter to Jean Claude Juncker, president of European Commision” (Hyderabad, Chennai, 2 July 2018).
3. AMR Industry Alliance, Tracking Progress to Address AMR(Geneva, January 2018).
Pharmaceutical Technology Europe
Vol. 30, No. 7
When referring to this article, please cite it as S. Milmo, “Pharmaceuticals in the Environment,” Pharmaceutical Technology Europe 30 (7) 2018.